Mutational analysis of gap junction formation

Dahl, Gerhard; Werner, Rudolf; Levine, Eric S.; Rabadan‐Diehl, Cristina

doi:10.1016/s0006-3495(92)81803-9

Cited by 152 publications

(120 citation statements)

References 26 publications

(37 reference statements)

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“…However, this expectation was only partially fulfilled. Binding of peptides to connexons did not open them so that a nonjunctional conductance would develop (13). However, the peptides did attenuate gap junction channel formation (11,13,44).…”

mentioning

confidence: 97%

“…GAP JUNCTION MIMETIC PEPTIDES were originally designed to mimic the docking gate of gap junction channels (11,13). Gap junctions in vertebrates typically are composed of connexins, which form hexameric connexons (22,41,45).…”

mentioning

confidence: 99%

“…Upon docking of two connexons residing in apposed cell membranes, the complete gap junction channel forms and opens. The docking process involves the two extracellular loops of the connexin protein (11,13,45). It was expected that peptides with sequences contained in these loops would mimic the homophilic looploop interaction and activate the docking gate.…”

mentioning

confidence: 99%

“…Binding of peptides to connexons did not open them so that a nonjunctional conductance would develop (13). However, the peptides did attenuate gap junction channel formation (11,13,44). This inhibition was connexin specific and gave rise to the development of a series of inhibitors of gap junction formation by the various connexins (18,26).…”

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confidence: 99%

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Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters

Wang¹,

Ma²,

Locovei³

et al. 2007

American Journal of Physiology-Cell Physiology

181

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. Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am J Physiol Cell Physiol 293: C1112-C1119, 2007. First published July 27, 2007; doi:10.1152/ajpcell.00097.2007.-Connexin mimetic peptides are widely used to assess the contribution of nonjunctional connexin channels in several processes, including ATP release. These peptides are derived from various connexin sequences and have been shown to attenuate processes downstream of the putative channel activity. Yet so far, no documentation of effects of peptides on connexin channels has been presented. We tested several connexin and pannexin mimetic peptides and observed attenuation of channel currents that is not compatible with sequence specific actions of the peptides. Connexin mimetic peptides inhibited pannexin channel currents but not the currents of the channel formed by connexins from which the sequence was derived. Pannexin mimetic peptides did inhibit pannexin channel currents but also the channels formed by connexin 46. The same pattern of effects was observed for dye transfer, except that the inhibition levels were more pronounced than for the currents. The channel inhibition by peptides shares commonalities with channel effects of polyethylene glycol (PEG), suggesting a steric block as a mechanism. PEG accessibility is in the size range expected for the pore of innexin gap junction channels, consistent with a functional relatedness of innexin and pannexin channels.

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confidence: 97%

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confidence: 99%

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confidence: 99%

mentioning

confidence: 99%

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Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters

Wang¹,

Ma²,

Locovei³

et al. 2007

American Journal of Physiology-Cell Physiology

181

205

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“…Currently, many residues within Cx43 have been linked to a certain function. The six cysteine residues within the two extracellular loops, which are found in all connexin protein family members, have been implicated in intercellular docking of connexons (Dahl et al 1992). These residues are conserved between all species.…”

Section: Resultsmentioning

confidence: 99%

Connexin43 orthologues in vertebrates: phylogeny from fish to man

et al. 2004

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The gap junction protein connexin43 (Cx43) is widely expressed in all vertebrate species; however, in ventricular myocardium, Cx43 expression is restricted to mammalian species only, where it provides the molecular correlate for both electrical conduction and synchronization of the repolarization process. The evolutionarily "late" appearance of Cx43 in the heart suggests physiological adaptation to euthermia with its concomitant demands related to increased cardiovascular output. We tested to what extent mammalian Cx43 differs from that of non-mammalian vertebrates and whether Cx43 from hibernating species contains specific sequence characteristics which could be attributed to their non-isothermal life cycle. We cloned the complete coding region of Cx43 from the African green monkey, European hedgehog (hibernator), Russian dwarf hamster, rabbit, European ground squirrel (hibernator) and pig. After sequencing, these were compared to 12 full-length Cx43 sequences present in GenBank (3 fish, 2 frogs, chicken and 6 mammals amongst which there was one other hibernator). Overall identity ranged from 68.7% to 97.7% at the nucleotide level and from 71.6% to 99.7% at the amino acid level. The phylogeny of Cx43 mirrors the general phylogenetic histories of the investigated species to a large extent. From 382 amino acids there were only 6 specific for mammals. There were no substitutions specific for hibernators. In conclusion, mammalian Cx43 is characterized by 6 specific amino acids, and no obvious differences between non-hibernating and hibernating mammals were observed.

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Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-tooth neuropathy

1996

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We studied the relationship between the genotype and clinical phenotype in 27 families with dominant X‐linked Charcot‐Marie‐Tooth (CMTX1) neuropathy. Twenty‐two families showed mutations in the coding region of the connexin32 (cx32) gene. The mutations include four nonsense mutations, eight missense mutations, two medium size deletions, and one insertion. Most missense mutations showed a mild clinical phenotype (five out of eight), whereas all nonsense mutations, the larger of the two deletions, and the insertion that produced frameshifts showed severe phenotypes. Five CMTX1 families with mild clinical phenotype showed no point mutations of the cx32 gene coding region. Three of these families showed positive genetic linkage with the markers of the Xq13.1 region. The genetic linkage of the remaining two families could not be evaluated because of their small size. © 1996 Wiley‐Liss, Inc.

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Mutational analysis of gap junction formation

Cited by 152 publications

References 26 publications

Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters

Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters

Connexin43 orthologues in vertebrates: phylogeny from fish to man

Correlation between connexin 32 gene mutations and clinical phenotype in X-linked dominant Charcot-Marie-tooth neuropathy

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